number of access : ?
number of downloads : ?
ID 106068
Title Alternative
低フコース化抗HM1.24抗体とレナリドミドの併用は骨髄腫細胞および骨髄腫細胞幹細胞に著明なADCC活性を示す
Combination of Defucosylated AHM plus Lenalidomide
Author
Harada, Takeshi Department of Medicine and Bioregulatory Sciences, Graduate School of Medical Sciences, University of Tokushima Tokushima University Educator and Researcher Directory
Ozaki, Shuji Tokushima Prefectural Central Hospital
Oda, Asuka University of Tokushima
Ikegame, Akishige Tokushima University
Iwasa, Masami University of Tokushima
Udaka, Kengo University of Tokushima
Kuroda, Yoshiaki Hiroshima University
Kawai, Shigeto Forerunner Pharma Research Co. Ltd.
Yamada-Okabe, Hisafumi Chugai Pharmaceutical Co. Ltd.
Keywords
Multiple myeloma
HM1.24
Lenalidomide
ADCC
Content Type
Thesis or Dissertation
Description
The immunomodulatory drug lenalidomide (Len) has drawn attention to potentiate antibody-dependent cellular cytotoxicity (ADCC)-mediated immunotherapies. We developed the defucosylated version (YB-AHM) of humanized monoclonal antibody against HM1.24 (CD317) overexpressed in multiple myeloma (MM) cells. In this study, we evaluated ADCC by YB-AHM and Len in combination against MM cells and their progenitors. YB-AHM was able to selectively kill via ADCC MM cells in bone marrow samples from patients with MM with low effector/target ratios, which was further enhanced by treatment with Len. Interestingly, Len also up-regulated HM1.24 expression on MM cells in an effector-dependent manner. HM1.24 was found to be highly expressed in a drug-resistant clonogenic ‘‘side population’’ in MM cells; and this combinatory treatment successfully reduced SP fractions in RPMI 8226 and KMS-11 cells in the presence of effector cells, and suppressed a clonogenic potential of MM cells in colony-forming assays. Collectively, the present study suggests that YB-AHM and Len in combination may become an effective therapeutic strategy in MM, warranting further study to target drug-resistant MM clonogenic cells.
Journal Title
PLOS ONE
ISSN
19326203
Publisher
PLOS
Volume
8
Issue
12
Start Page
e83905
Published Date
2013-12-26
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201404221012.pdf
論文本文 : LID201405281001.pdf
本論文は, 著者Takeshi Haradaの学位論文として提出され, 学位審査・授与の対象となっている。
Rights
Copyright: © 2013 Harada et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.( https://creativecommons.org/licenses/by/4.0/ )
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2668号
Diploma Number
甲医第1188号
Granted Date
2014-03-24
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Pharmaceutical Sciences
Medical Sciences
Institute of Advanced Medical Sciences